Immunotherapy Slows Tumor Growth in Prostate Cancer Model

Cancer researchers have developed a novel immunotherapy technique based on synthetic DNA plasmids that successfully controlled tumor growth and prolonged survival in a mouse prostate cancer model.

The protein prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate cancer. Current immunotherapy approaches to target PSMA include peptide, cell, vector, or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life.

In order to overcome the problem of short mAb half-life in circulation, investigators at The Wistar Institute (Philadelphia, PA, USA) devised a novel strategy of antibody-based immunotherapy that utilized synthetic DNA plasmids to encode a therapeutic human mAb that targeted PSMA. The DNA in the plasmids enabled the host animal to produce the therapeutic mAb in a sustained manner.

The investigators reported in the August 17, 2017, online edition of the journal Cancer Immunology, Immunotherapy that electroporation-enhanced intramuscular injection of the DNA-encoded mAb (DMAb) plasmids into mice led to the production of functional and durable levels of the anti-PSMA antibody. The anti-PSMA produced in vivo controlled tumor growth and prolonged survival in the mouse model. The healing effect was likely mediated by antibody-dependent cellular cytotoxicity (ADCC) with the aid of NK (natural killer) cells.

"This is an important demonstration of the possibilities opened up for immunotherapy by DMAb technology to direct in vivo production of antibodies of major relevance to human cancer," said senior author Dr. David B. Weiner, director of the Vaccine & Immunotherapy Center at The Wistar Institute. "There is a great need for such new approaches for prostate disease as well as many other cancers. As recent data suggest, PSMA is an important cancer antigen expressed on many human prostate, bladder, renal as well as ovarian cancers, so additional study of the possible benefits of this therapy are important."

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